title: Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids.
abstract: OBJECTIVE
  We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based on routinely available clinical and laboratory data.
  
  
  METHODS
  We analysed the concentrations of molecular lipids by UPLC-MS in blood samples of 679 well-characterised individuals in whom liver-fat content was measured using proton magnetic resonance spectroscopy ((1)H-MRS) or liver biopsy. The participants were divided into biomarker-discovery (n = 287) and validation (n = 392) groups to build and validate the diagnostic models, respectively.
  
  
  RESULTS
  Individuals with NAFLD had increased triacylglycerols with low carbon number and double-bond content while lysophosphatidylcholines and ether phospholipids were diminished in those with NAFLD. A serum-lipid signature comprising three molecular lipids ('lipid triplet') was developed to estimate the percentage of liver fat. It had a sensitivity of 69.1% and specificity of 73.8% when applied for diagnosis of NAFLD in the validation series. The usefulness of the lipid triplet was demonstrated in a weight-loss intervention study.
  
  
  CONCLUSIONS
  The liver-fat-biomarker signature based on molecular lipids may provide a non-invasive tool to diagnose NAFLD, in addition to highlighting lipid molecular pathways involved in the disease.
authors.affiliation: VTT Technical Research Centre of Finland, Tietotie 2, PO Box 1000, Espoo, 02044 VTT, Finland. matej.oresic@vtt.fi
authors.forename: Matej
authors.initials: M
authors.lastname: Orešič
authors.forename: Tuulia
authors.initials: T
authors.lastname: Hyötyläinen
authors.forename: Anna
authors.initials: A
authors.lastname: Kotronen
authors.forename: Peddinti
authors.initials: P
authors.lastname: Gopalacharyulu
authors.forename: Heli
authors.initials: H
authors.lastname: Nygren
authors.forename: Johanna
authors.initials: J
authors.lastname: Arola
authors.forename: Sandra
authors.initials: S
authors.lastname: Castillo
authors.forename: Ismo
authors.initials: I
authors.lastname: Mattila
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.forename: Ronald J H
authors.initials: RJ
authors.lastname: Borra
authors.forename: Miikka-Juhani
authors.initials: MJ
authors.lastname: Honka
authors.forename: An
authors.initials: A
authors.lastname: Verrijken
authors.forename: Sven
authors.initials: S
authors.lastname: Francque
authors.forename: Patricia
authors.initials: P
authors.lastname: Iozzo
authors.forename: Marja
authors.initials: M
authors.lastname: Leivonen
authors.forename: Nabil
authors.initials: N
authors.lastname: Jaser
authors.forename: Anne
authors.initials: A
authors.lastname: Juuti
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Pirjo
authors.initials: P
authors.lastname: Nuutila
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005234:Fatty Liver / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008055:Lipids / Q000097:blood*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D055815:Young Adult
chemical_list: D008055:Lipids